The use of ultrasound in vascular procedures.

While the use of duplex ultrasound (DUS) in the diagnosis of vascular disease has been established, its role in vascular procedures continues to expand. More powerful and portable technology has helped to overcome real and perceived barriers to the use of DUS. Familiarity with Doppler and ultrasound physics is helpful to understand the potential roles and limitations of DUS. Use of real-time imaging allows the surgeon to obtain central venous and peripheral arterial access, as well as place vena cava filters and treat iatrogenic arterial pseudoaneurysms with a greater degree of patient safety, comfort, and overall success.

Circulating regulatory T cells (CD4+CD25+FOXP3+) decrease in breast cancer patients after vaccination with a modified MHC class II HER2/neu (AE37) peptide.

Regulatory T cells (T(Reg)), CD4(+)CD25(+)FOXP3(+), are implicated in suppressing tumor immune responses. We analyzed peripheral blood lymphocytes (PBL) from breast cancer patients receiving a modified HLA class II HER2/neu peptide (AE37) vaccine for T(Reg) cells and correlated their levels with vaccine-specific immune responses. The mean CD4(+)CD25(+)FOXP3(+) T(Reg) cells decreased in patients with vaccination with no significant difference in serum TGF-ß levels. IFN-γ ELISPOT and DTH increased after vaccination with a good correlation between T(Reg) cell reduction and size of DTH to AE37. The T(Reg) cell reduction and associated immune response suggest that AE37 may be clinically useful.

Combined clinical trial results of a HER2/neu (E75) vaccine for the prevention of recurrence in high-risk breast cancer patients: U.S. Military Cancer Institute Clinical Trials Group Study I-01 and I-02.

PURPOSE: E75 is an immunogenic peptide from the HER2/neu protein, which is overexpressed in many breast cancer patients. We have conducted two overlapping E75 vaccine trials to prevent recurrence in node-positive (NP) and node-negative (NN) breast cancer patients. EXPERIMENTAL DESIGN: E75 (HER2/neu 369-377) + granulocyte macrophage colony-stimulating factor was given intradermally to previously treated, disease-free NP breast cancer patients in a dose escalation safety trial and to NN breast cancer patients in a dose optimization study. Local and systemic toxicity was monitored. Immunologic responses were assessed using in vitro assays and in vivo delayed-type hypersensitivity responses. Clinical recurrences were documented. RESULTS: One hundred and eighty-six patients were enrolled in the two studies (NP, 95; NN, 91). Human leucocyte antigen A2 (HLA-A2) and HLA-A3 patients were vaccinated (n = 101), whereas all others (n = 85) were followed prospectively as controls. Toxicities were minimal, and a dose-dependent immunologic response to the vaccine was shown. Planned primary analysis revealed a recurrence rate of 5.6% in vaccinated patients compared with 14.2% in the controls (P = 0.04) at a median of 20 months follow-up. As vaccine-specific immunity waned over time, the difference in recurrence lost significance at 26 months median follow-up (8.3% versus 14.8%); however, a significant difference in the pattern of recurrence persisted. CONCLUSIONS: E75 is safe and effective in raising a dose-dependent HER2/neu immunity in HLA-A2 and HLA-A3 NP and NN breast cancer patients. More importantly, E75 may reduce recurrences in disease-free, conventionally treated, high-risk breast cancer patients. These findings warrant a prospective, randomized phase III trial of the E75 vaccine with periodic booster to prevent breast cancer recurrences.

Pattern of serum immunoreactivity against breast cancer cell lysates may predict severity of disease in breast cancer patients.

Humoral tumor-specific immunity has been investigated as a potential tool to identify tumor-associated antigens and evaluate cancer diagnosis and prognosis. Using SDS-PAGE and western blotting techniques we investigated the humoral immune response against tumor cell antigens in 36 breast cancer patients, 17 node-positive (NP) and 19 node-negative (NN). As a source of antigens, we prepared protein lysates from four breast cancer cell lines (AU565, BT474, MCF-7 and MDA-MB-231) which in vitro exhibit different features of invasion, estrogen receptor/progesterone receptor status and HER2/neu expression thereby potentially representing mild to aggressive forms of clinical disease. A higher number of immunocomplexes Ag-Ab were formed when serum from NN patients was immunoreacted against lysates from AU565 and MCF-7 in comparison to serum from NP patients (P < 0.01). BT474 cells were not a good antigenic source. MDA-MB-231 cells could not significantly discriminate between NN and NP patients since both groups showed higher amounts of reactivity against the lysate. However, comparative analysis of protein preparations purified from MCF-7 and MDA-MB-231 cells and immunodetected concomitantly with the same serum samples showed that serum from patients with cancers with worse prognosis (stage, nodality, HER2/neu and hormonal status) reacted more intensely to proteins purified from the relatively more invasive cell line MDA-MB-231 compared to MCF-7. These findings suggest that the study of serum antibody reactivity to antigens purified from breast cancer cell lines with different invasive properties should be further investigated for its potential in providing beneficial prognostic information in breast cancer.

HER2/neu vaccines in breast cancer.

Recently, the role of immunotherapy has been expanded in the management of breast cancer. The human epidermal growth factor receptor (HER)2/neu protein is overexpressed in many breast cancers, and is the target of documented endogenous immune responses. To exploit these responses, several immunotherapies have been developed, such as trastuzumab, a monoclonal antibody targeting this protein, as well as several HER2/neu-based vaccines. Clinical studies in metastatic patients have shown these vaccines to be safe and to produce vaccine-specific immune responses; unfortunately, little evidence of clinical effectiveness has been reported. The authors' group has evaluated a HER2/neu vaccine as a preventive adjunct in breast cancer patients who are disease free but at a high risk of recurrence. Preliminary results suggest a decrease in recurrence and imply that vaccinating earlier in the disease process may hold promise. In the future, vaccine therapy, alone or in combination, could be a valuable preventive modality in the management of breast cancer.